Figure 4. Flow-mediated formation of thick VWF fibres and meshes in grid vessels.

(a) z-section projection of secreted VWF in a grid vessel network for −20 μm <z <20 μm (z=0 at the centre plane between the top and bottom walls of the vessel) showing that transluminal fibres formed predominantly near the inlet and outlet regions of the grid. Region (i) corresponds to panel d and (ii) corresponds to panel e. (b) COMSOL simulation of flow at the centre cross-sectional plane of the grid vessel. Colour map: flow speed. (c) Correlation between the shear rate and the amount of secreted VWF (C.1) or the presence of VWFtransluminal fibres (0: no VWF-transluminal fibres and 1: presence of VWF-transluminal fibres). Red: converging vessel branches (towards outlet) and blue: diverging vessel branches (near inlet). ***P<0.001 with paired t-test. (d,e) Zoomed-in view shows the flow-induced formation of (d) VWF strands entangled at the vessel junctions near the inlet and (e) a VWF web at the centre stream of a vessel branch near the outlet. (f–h) Confocal z-projection images of an activated grid vessel near the inlet (f, the dashed arrow points to a box that shows the yz-projected image at the dashed line), at the bifurcation of the inlet (g), and at the outlet (h, xy-plane projection in the bottom panel and yz-plane projection in the top panel). Arrowheads: merging of multiple VWF strands to thicker strands; asterisks: two VWF strands that originate near each other travelling in different directions at the bifurcation. Red: CD31, green: VWF and blue: nuclei. N >10.